{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:16:12Z","timestamp":1785507372399,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"United States Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1I21RX004101-01"],"award-info":[{"award-number":["1I21RX004101-01"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"award":["1I21RX004101-01"],"award-info":[{"award-number":["1I21RX004101-01"]}],"id":[{"id":"https:\/\/ror.org\/05rsv9s98","id-type":"ROR","asserted-by":"publisher"}]},{"name":"The University of Nevada, Reno School of Medicine Clinical Research Pilot Funding PLUS+ Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Thiamine deficiency (TD) causes thiamine deficiency disorders (TDDs) which are frequently overlooked in food-secure countries such as the United States (U.S.). Lack of awareness and the absence of validated, rapidly available biomarkers perpetuate underdiagnosis. Our objective was to determine prevalence of TD in hospitalized U.S. veterans without alcohol use disorder (AUD) and describe clinical characteristics of TDDs. A secondary objective was to evaluate the utility of plasma and whole-blood thiamine biomarkers in identifying thiamine-responsive disorders (TRDs). Methods: Newly hospitalized veterans without AUD were recruited. Fasting plasma and whole-blood thiamine were obtained. Interview, physical exam, and chart review were completed to assess clinical signs of TD. Participants were invited to return after thiamine repletion and changes in symptoms and exam findings were noted. Results: A total of 286 participants were enrolled: 261 had plasma thiamine results, 259 had whole-blood thiamine results, 179 completed interviews, 164 completed initial examination, and 60 returned for reexamination after repletion. A majority (86.59%) had potential signs or symptoms of TDDs, 26.44% had low plasma thiamine, 2.70% had low whole-blood thiamine, and 97.92% with low plasma thiamine had clinical signs of TDDs and many experienced multiple TD syndromes. Those with low plasma thiamine who returned after repletion showed improvements in cognitive scores (p = 0.0093) and motor strength (p = 0.0417), and most reported symptom improvement. Whole-blood thiamine missed many cases of TRDs. Conclusions: TD affects one quarter of hospitalized veterans without AUD. Low plasma thiamine identifies TRDs more frequently than low whole-blood thiamine. Using clinical criteria alone to diagnose TDDs overestimates cases and biomarker confirmation appears necessary.<\/jats:p>","DOI":"10.3390\/diseases14080275","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T13:23:20Z","timestamp":1785504200000},"page":"275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Thiamine Deficiency in Hospitalized Veterans Without Alcohol Use Disorder: Prevalence, Biomarker Assessment, and Clinical Characteristics"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9267-1869","authenticated-orcid":false,"given":"Elisabeth A.","family":"Mates","sequence":"first","affiliation":[{"name":"Department of Medicine, VA Sierra Nevada Healthcare System, Reno, NV 89502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandrea","family":"Kilgore-Gomez","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4973-3379","authenticated-orcid":false,"given":"Claire","family":"Phibbs","sequence":"additional","affiliation":[{"name":"Department of Research & Development, VA Sierra Nevada Healthcare System, Reno, NV 89502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","unstructured":"Shils, M., Shike, M., Ross, A., Caballero, B., and Cousins, R. (2006). Thiamin. Modern Nutrition in Health and Disease, Lippincott Williams & Wilkins. [10th ed.]. Chapter 23."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/j.clnu.2022.02.015","article-title":"ESPEN micronutrient guideline","volume":"41","author":"Berger","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1021\/bi401618y","article-title":"Thiamin function, metabolism, uptake, and transport","volume":"53","author":"Manzetti","year":"2014","journal-title":"Biochemistry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"BSR20230374","DOI":"10.1042\/BSR20230374","article-title":"The importance of thiamine (vitamin B1) in humans","volume":"43","author":"Mrowicka","year":"2023","journal-title":"Biosci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/nyas.14536","article-title":"Thiamine Deficiency Disorders: A Clinical Perspective","volume":"1498","author":"Smith","year":"2021","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/nyas.13919","article-title":"Thiamine deficiency disorders: Diagnosis, prevalence, and a roadmap for global control programs","volume":"1430","author":"Whitfield","year":"2018","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1111\/j.1468-1331.2010.03153.x","article-title":"EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy","volume":"17","author":"Galvin","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s10545-014-9712-9","article-title":"Defects of thiamine transport and metabolism","volume":"37","author":"Brown","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1515\/cclm-2017-0054","article-title":"Vitamin B1 in critically ill patients: Needs and challenges","volume":"55","author":"Collie","year":"2017","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Dhir, S., Tarasenko, M., Napoli, E., and Giulivi, C. (2019). Neurological, psychiatric, and biochemical aspects of thiamine deficiency in children and adults. Front. Psychiatry, 10.","DOI":"10.3389\/fpsyt.2019.00207"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/jn\/108.3.421","article-title":"The Determination of Thiamin Pyrophosphate in Blood and Other Tissues, and Its Correlation with Erythrocyte Transketolase Activity","volume":"108","author":"Warnock","year":"1978","journal-title":"J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/S1474-4422(07)70104-7","article-title":"Wernicke\u2019s encephalopathy: New clinical settings and recent advances in diagnosis and management","volume":"6","author":"Sechi","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"McCandless, D.W. (2009). Thiamine Deficiency and Associated Clinical Disorders, Humana Press.","DOI":"10.1007\/978-1-60761-311-4"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1111\/j.1468-1331.2011.03602.x","article-title":"Dry beriberi mimicking Guillain-Barre syndrome as the first presenting sign of thiamine deficiency","volume":"19","author":"Faigle","year":"2012","journal-title":"Eur. J. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Overton, E., Emelyanova, A., and Bunik, V.I. (2025). Thiamine, gastrointestinal beriberi and acetylcholine signaling. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1541054"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"503596","DOI":"10.1155\/2014\/503596","article-title":"MR imaging findings in alcoholic and nonalcoholic acute Wernicke\u2019s encephalopathy: A review","volume":"2014","author":"Manzo","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"117482","DOI":"10.1016\/j.jns.2021.117482","article-title":"Wernicke-Korsakoff syndrome despite no alcohol abuse: A summary of systematic reports","volume":"426","author":"Oudman","year":"2021","journal-title":"J. Neurol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.mayocp.2017.02.019","article-title":"Differences Between Alcoholic and Nonalcoholic Patients With Wernicke Encephalopathy: A Multicenter Observational Study","volume":"92","author":"Chamorro","year":"2017","journal-title":"Mayo Clin. Proc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1177\/1535370217750088","article-title":"Biomarker definitions and their applications","volume":"243","author":"Califf","year":"2018","journal-title":"Exp. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e36539","DOI":"10.1136\/bmjopen-2019-036539","article-title":"Establishing a case definition of thiamine responsive disorders among infants and young children in Lao PDR: Protocol for a prospective cohort study","volume":"10","author":"Hess","year":"2020","journal-title":"BMJ Open"},{"key":"ref_21","unstructured":"Preedy, V.R. (2012). Measurement of Thiamine Levels in Human Tissue. B Vitamins and Folate: Chemistry, Analysis, Function and Effects, The Royal Society of Chemistry."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1079\/BJN19940014","article-title":"Thiamine intake, erythrocyte transketolase activity and total erythrocyte thiamin in adolescents.pdf","volume":"72","author":"Bailey","year":"1994","journal-title":"Br. J. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e142","DOI":"10.1016\/S1470-2045(16)00037-1","article-title":"Wernicke-Korsakoff syndrome in patients with cancer: A systematic review","volume":"17","author":"Rahane","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.pathol.2023.11.002","article-title":"Biomarkers and biomarker validation: A pathologist\u2019s guide to getting it right","volume":"56","author":"Paver","year":"2024","journal-title":"Pathology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"174","DOI":"10.3122\/jabfm.2024.240224R1","article-title":"Interpretating Normal Values and Reference Ranges for Laboratory Tests","volume":"38","author":"Doles","year":"2025","journal-title":"J. Am. Board Fam. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.jtho.2021.01.1616","article-title":"Biomarker Discovery and Validation: Statistical Considerations","volume":"16","author":"Ou","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"103786","DOI":"10.1016\/j.cdnut.2024.103786","article-title":"Assessment of Erythrocyte Transketolase, Whole Blood Thiamine Diphosphate, and Human Milk Thiamine Concentrations to Identify Infants and Young Children Responding Favorably to Therapeutic Thiamine Administration: Findings from the Lao Thiamine Study, a Prospective Cohort Study","volume":"8","author":"Hess","year":"2024","journal-title":"Curr. Dev. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mates, E.A., Watkins, K., Sanchez, C., Fiore, N., and Phibbs, C. (2026). Thiamine and Micronutrient Deficiencies in Hospitalized Veterans Without Alcohol Use Disorder. Diseases, 14.","DOI":"10.3390\/diseases14030095"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"431","DOI":"10.3233\/JAD-190457","article-title":"The U-ARE Protocol: A Pragmatic Approach to Decisional Capacity Assessment for Clinical Research","volume":"73","author":"Hamilton","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jchromb.2018.07.030","article-title":"A single-step method for simultaneous quantification of thiamine and its phosphate esters in whole blood sample by ultra-performance liquid chromatography-mass spectrometry","volume":"1095","author":"Cheng","year":"2018","journal-title":"J. Chromatogr. B"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clnu.2018.08.002","article-title":"GLIM criteria for the diagnosis of malnutrition\u2014A consensus report from the global clinical nutrition community","volume":"38","author":"Cederholm","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1136\/jnnp.62.1.51","article-title":"Operational criteria for the classification of chronic alcoholics: Identification of Wernicke\u2019s encephalopathy","volume":"62","author":"Caine","year":"1997","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_33","unstructured":"Rosenthal, M.D., and Glew, R.H. (2009). Medical Biochemistry: Human Metabolism in Health and Disease, John Wiley and Sons Inc.. Available online: https:\/\/labalbaha.wordpress.com\/wp-content\/uploads\/2014\/04\/medical-biochemistry-human-metabolism-in-health-and-disease.pdf."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.nutres.2016.11.012","article-title":"Prevalence of clinical thiamine deficiency in individuals with medically complicated obesity","volume":"37","author":"Nath","year":"2017","journal-title":"Nutr. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1177\/0148607194018002104","article-title":"Nutritional and Metabolic Characterization of a Thiamine-Deficient Rat Model","volume":"18","author":"Molina","year":"1994","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.japh.2019.12.005","article-title":"Safety of intravenous push thiamine administration at a tertiary academic medical center","volume":"60","author":"McLaughlin","year":"2020","journal-title":"J. Am. Pharm. Assoc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s11065-012-9200-7","article-title":"Wernicke\u2019s encephalopathy: Expanding the diagnostic toolbox","volume":"22","author":"Lough","year":"2012","journal-title":"Neuropsychol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"120168","DOI":"10.1016\/j.talanta.2019.120168","article-title":"Periplasmic binding protein-based magnetic isolation and detection of thiamine in complex biological matrices","volume":"205","author":"Edwards","year":"2019","journal-title":"Talanta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1136\/jnnp.49.4.341","article-title":"Clinical signs in the Wernicke-Korsakoff complex: A retrospective analysis of 131 cases diagnosed at necropsy","volume":"49","author":"Harper","year":"1986","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3174\/ajnr.A1280","article-title":"MR Imaging Findings in 56 Patients with Wernicke Encephalopathy: Nonalcoholics May Differ from Alcoholics","volume":"30","author":"Zuccoli","year":"2009","journal-title":"Am. J. Neuroradiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"afac155","DOI":"10.1093\/ageing\/afac155","article-title":"Association between multimorbidity and hospitalization in older adults: Systematic review and meta-analysis","volume":"51","author":"Rodrigues","year":"2022","journal-title":"Age Ageing"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1001\/jamainternmed.2023.7410","article-title":"Population-Based Trends in Complexity of Hospital Inpatients","volume":"184","author":"Naik","year":"2024","journal-title":"JAMA Intern. Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Mates, E., Alluri, D., Artis, T., and Riddle, M.S. (2021). A Retrospective Case Series of Thiamine Deficiency in Non-Alcoholic Hospitalized Veterans: An Important Cause of Delirium and Falling?. J. Clin. Med., 10.","DOI":"10.3390\/jcm10071449"}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/8\/275\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T13:41:24Z","timestamp":1785505284000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/8\/275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":43,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["diseases14080275"],"URL":"https:\/\/doi.org\/10.3390\/diseases14080275","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]}}}